title: Insights into the protective mechanisms of tamoxifen in radiotherapy-induced ovarian follicular loss: impact on insulin-like growth factor 1.
abstract: Radiotherapy is one of the most common and effective cancer treatments. However, it has a profound impact on ovarian function, leading to premature ovarian failure. With the hope of preserving fertility in cancer survivors, the need for an effective radioprotective therapy is evident. The present study investigated the mechanism of the potential radioprotective effect of tamoxifen (TAM) on γ-irradiation-induced ovarian failure on experimental rats and the impact of the IGF-1 in the underlying protective mechanisms. Female Sprague Dawley rats were either exposed to single whole-body irradiation (3.2 Gy; lethal dose [LD₂₀]) and/or treated with TAM (1 mg/kg). γ-Irradiation caused an array of ovarian dysfunction that was evident by assessment of hormonal changes, follicular development, proliferation marker (proliferating cell nuclear antigen), and oxidative stress as well as apoptotic markers. In addition, IGF-1/IGF-1 receptor axis expression was assessed using real-time RT-PCR and immunolocalization techniques. Furthermore, fertility assessment was performed. TAM significantly enhanced follicular development and restored the anti-Mullerian hormone level. Moreover, it ameliorated the deleterious effects of irradiation on oxidative stress, proliferating cell nuclear antigen expression, and apoptosis. Interestingly, TAM was shown to enhance the ovarian IGF-1 but not IGF-1 receptor, a property that contributed significantly to its radioprotective mechanisms. Finally, TAM regained the fertility that was lost after irradiation. In conclusion, TAM showed a radioprotective effect and saved the ovarian reserve and fertility through increasing anti-Mullerian hormone and the local IGF-1 level and counteracting the oxidative stress-mediated apoptosis.
authors.affiliation: Professor of Pharmacology and Toxicology, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt. ebtehal_dm@yahoo.com or ebtehal_dm@pharma.asu.edu.
authors.forename: Yasmen F
authors.initials: YF
authors.lastname: Mahran
authors.forename: Ebtehal
authors.initials: E
authors.lastname: El-Demerdash
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Nada
authors.forename: Azza A
authors.initials: AA
authors.lastname: Ali
authors.forename: Ashraf B
authors.initials: AB
authors.lastname: Abdel-Naim
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000097:blood; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D005260:Female; D005720:Gamma Rays; D007247:Infertility, Female / Q000209:etiology / Q000517:prevention & control; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D018384:Oxidative Stress / Q000187:drug effects; D016649:Primary Ovarian Insufficiency / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects*; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D015415:Biomarkers; D011837:Radiation-Protective Agents; D020845:Selective Estrogen Receptor Modulators; C548904:insulin-like growth factor-1, rat; D013629:Tamoxifen; D007334:Insulin-Like Growth Factor I; D054304:Anti-Mullerian Hormone; D017526:Receptor, IGF Type 1